The proposed work involves stopped-flow kinetics studies of ionic strength-dependent electron transfer reactions between transition metal complex (small molecule) redox agents and cytochrome c derivatives chemically modified to neutralize charges on specific protein surface residues. This work will help characterize the involvement of electrostatic effects in the electron transfer reactions of cytochrome c, as evidenced by the ionic strength dependence of the physiological electron transfer reactions of this protein (e.g., with cytochrome c oxidase). Specifically, the main goals will be: (1) to detemine the region of the surface of cytochrome c at which a series of small molecule redox agents interact and the similarity between this region and the analogous physiologically important region; (2) to develop a semi-empirical description of the mathematical form of the ionic strength dependence taking into account the known spatial distribution of suface charges on cytochrome c. The information to be gained from these studies will be of critical importance in understanding the detailed nature of the involvement of electrostatic effects in biological electron transfer processes and will also constitute a test of the assumption that the inorganic small molecule redox agents can model the physiological electron transfer mechanisms employed by cytochrome c.